Genetic Variant NM_016029.4:c.698G>T (chr14-60150123-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016029.4(DHRS7):c.698G>T(p.Cys233Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 1,568,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C233S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

DHRS7
NM_016029.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.919

Publications

0 publications found

Variant links:

Genes affected

DHRS7 (HGNC:21524): (dehydrogenase/reductase 7) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family, which has over 46,000 members. Members in this family are enzymes that metabolize many different compounds, such as steroid hormones, prostaglandins, retinoids, lipids and xenobiotics. [provided by RefSeq, Apr 2016]

DHRS7 links:

PCNX4 (HGNC:20349): (pecanex 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PCNX4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016029.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DHRS7	NM_016029.4	MANE Select	c.698G>T	p.Cys233Phe	missense	Exon 5 of 7	NP_057113.1	Q9Y394-1
DHRS7	NM_001322280.2		c.548G>T	p.Cys183Phe	missense	Exon 5 of 7	NP_001309209.1	Q9Y394-2
DHRS7	NM_001322282.2		c.458G>T	p.Cys153Phe	missense	Exon 4 of 6	NP_001309211.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DHRS7	ENST00000557185.6	TSL:1 MANE Select	c.698G>T	p.Cys233Phe	missense	Exon 5 of 7	ENSP00000451882.1	Q9Y394-1
DHRS7	ENST00000536410.6	TSL:1	c.548G>T	p.Cys183Phe	missense	Exon 5 of 7	ENSP00000442993.2	Q9Y394-2
DHRS7	ENST00000554101.5	TSL:2	c.680G>T	p.Cys227Phe	missense	Exon 5 of 6	ENSP00000450899.1	H0YJ66

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

134314

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000238

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000156

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000820

AC:

AN:

243846

AF XY:

0.00000757

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000558

AC:

AN:

1434036

Hom.:

Cov.:

AF XY:

0.00000421

AC XY:

AN XY:

713270

show subpopulations

African (AFR)

AF:

0.000188

AC:

AN:

31836

American (AMR)

AF:

0.00

AC:

AN:

42912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25088

East Asian (EAS)

AF:

0.00

AC:

AN:

37060

South Asian (SAS)

AF:

0.0000119

AC:

AN:

83708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

9.11e-7

AC:

AN:

1097226

Other (OTH)

AF:

0.00

AC:

AN:

58534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000447

AC:

AN:

134314

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

64496

show subpopulations

African (AFR)

AF:

0.000116

AC:

AN:

34574

American (AMR)

AF:

0.00

AC:

AN:

12620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3318

East Asian (EAS)

AF:

0.00

AC:

AN:

4518

South Asian (SAS)

AF:

0.000238

AC:

AN:

4196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

248

European-Non Finnish (NFE)

AF:

0.0000156

AC:

AN:

64256

Other (OTH)

AF:

0.00

AC:

AN:

1806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000843

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

Eigen

Benign

0.069

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.70

M_CAP

Benign

0.066

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.4

PhyloP100

0.92

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-9.0

REVEL

Uncertain

0.34

Sift

Benign

0.062

Sift4G

Uncertain

0.011

Polyphen

0.97

Vest4

0.46

MutPred

0.63

Loss of catalytic residue at C233 (P = 0.1339)

MVP

0.64

MPC

0.071

ClinPred

0.87

GERP RS

0.0035

Varity_R

0.43

gMVP

0.73

Mutation Taster

=62/38

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over